[unreadable] This proposal for OPD sponsorship applies autologous gene-modified T cells in a new type of immuno-gene therapy for gastric cancer. The investigators created chimeric IgTCR as molecular fusion products of a single chain humanized anti-CEA antibody (Ab) binding domain with the zeta signaling chain of the TCR. When expressed by gene therapy techniques in recipient T cells, the resulting "designer T cells" combine the specificity of Ab with the cytotoxic potency of T cells. CEA is expressed at high levels on >80% of gastric cancers, with only minor expression on normal tissues, making CEA a suitable antigen (Ag) for targeting gastric carcinomas. Gastric cancer has a U.S. prevalence of 20,000 patients and takes 12,000 lives annually in the United States; no presently available therapy can cure patients with metastatic disease. Therefore, a cellular therapy against gastric cancer would offer a new therapeutic option to these patients. [unreadable] [unreadable] The investigators previously performed a Phase 1 trial with first generation designer T cells that yield Signal 1 (TCR) on tumor contact. This study showed adequate patient tolerance and yielded preliminary indications of efficacy, but of limited duration. In vitro correlates suggested that activation-induced cell death (AICD) contributed to lack of in vivo persistence of the infused T cells. This prompted a product redesign to add CD28 co-stimulation (Signal 2) on tumor contact via an IgCD28TCR. In preclinical tests, these second generation (2nd gen) designer T cells with Signal 1+2 resisted AICD, with improved survival on contact with CEA+ tumor targets, resulting in superior anti-tumor activity in vitro and in vivo in animal models. Specific Aims are the following: (1) to conduct Phase 1 trial of 2nd gen designer T cells, a. to assess safety (toxicity/tolerance), and establish maximum tolerated dose/maximum practical dose (MTD/MPD); (2) to assess pharmacokinetics, pharmacodynamics and incidental measures of response. Phase 2 efficacy tests will follow in the post-award period. The hypothesis is that the addition of Signal 2 stimulation will improve the potency and duration of designer T cell action without serious treatment-related toxicities. The investigators anticipate that the survival advantage of these 2nd gen anti-CEA T cells will ultimately translate into extended clinical responses in patients with advanced gastric carcinomas. [unreadable] [unreadable] [unreadable]